Machine Learning-Based Radiomics Analysis for Identifying KRAS Mutations in Non-Small-Cell Lung Cancer from CT Images: Challenges, Insights and Implications

Kirsten Rat Sarcoma viral oncogene homolog (KRAS) is a frequently occurring mutation in non-small-cell lung cancer (NSCLC) and influences cancer treatment and disease progression. In this study, a machine learning (ML) pipeline was applied to radiomic features extracted from public and internal CT images to identify KRAS mutations in NSCLC patients. Both datasets were analyzed using parametric ( test) and non-parametric statistical tests (Mann-Whitney U test) and dimensionality reduction techniques. Afterwards, the proposed ML pipeline was applied to both datasets using a five-fold cross-validation on the training set (70/30 train/test split) before being validated on the other dataset. The results show that the radiomic features are significantly different (Mann-Whitney U test; < 0.05) between the two datasets, despite the use of identical feature extraction methods. Model transferability is therefore difficult to achieve, which became evident during external testing (F1 score = 0.41). Oversampling, undersampling, clustering and harmonization techniques were applied to balance and harmonize the datasets, but did not improve the classification of KRAS mutation presence. In general, due to only a single moderate result (highest test F1 score = 0.67), the accuracy of KRAS prediction is not sufficient for clinical application. In future work, the complexity of KRAS mutation might be addressed by taking submutations into consideration. Larger multicentric datasets with balanced tumor stages, including multi-scanner datasets, seem to be necessary for building robust predictive models.